Molecular pathology and clinical implications of diffuse glioma

Chai, Rui‐Chao; Sun, Fang; Pang, Bo; Liu, Yuqing; Wang, Yongzhi; Zhang, Wei; Jiang, Tao

doi:10.1097/cm9.0000000000002446

Cited by 16 publications

(14 citation statements)

References 79 publications

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“…Previous studies have associated the molecular features of glioma with clinical classification. Patients with glioma without IDH mutant or 1p/19q co‐deleted had worse outcomes 62–64 . In addition, tumors with different IDH and 1p/19q status undergo distinct cell‐state changes at recurrence, which may interfere with the comparison of the microenvironment between primary gliomas and recurrent gliomas.…”

Section: Discussionmentioning

confidence: 99%

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

et al. 2023

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AimsTumor‐associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2‐like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence.MethodsWe employed single‐cell RNA sequencing to construct a single‐cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma.ResultsSix subgroups of TAMs were annotated and M2‐like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up‐regulation of several cancer pathways and intercellular interaction‐related genes are associated with the recurrence of malignant glioma. Moreover, the M2‐like TAMs can activate the PI3K/Akt/HIF‐1α/CA9 pathway in the malignant glioma cells via SPP1‐CD44‐mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance.ConclusionOur study uncovers the distinction of M2‐like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma.

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Section: Discussionmentioning

confidence: 99%

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

et al. 2023

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“…[8] Despite a combination of surgery, radiotherapy, chemotherapy, targeted therapy and supportive care, the prognosis of glioma patients remains poor. [9,10] The worldwide median survival time for patients with lowgrade glioma (LGG) is 5.6-13.3 years and for patients with high-grade glioma (HGG), it is only 12.2-15.4 months. [11][12][13] Stress is a regular part of daily life.…”

Section: Introductionmentioning

confidence: 99%

Chronic stress as an emerging risk factor for the development and progression of glioma

Yi,

Lin,

She

et al. 2024

Chinese Medical Journal

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Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system. Compared with patients with other cancers, glioma patients often suffer from increased levels of psychological stress, such as anxiety and fear. Chronic stress (CS) is thought to impact glioma profoundly. However, because of the complex mechanisms underlying CS and variability in individual tolerance, the role of CS in glioma remains unclear. This review suggests a new proposal to redivide the stress system into two parts. Neuronal activity is dominant upstream. Stress-signaling molecules produced by the neuroendocrine system are dominant downstream. We discuss the underlying molecular mechanisms by which CS impacts glioma. Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.

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“…We present two novel cases of pediatric glioneuronal tumors with a CLIP2 :: MET fusion detected by whole transcriptome sequencing (RNAseq), along with their clinical, pathologic, and molecular findings. While the CLIP2 :: MET fusion has been previously reported in three instances, including an adult glioneuronal tumor [ 8 ], a case of spontaneous regression of a congenital high-grade glioma [ 18 ], and at least two cases of infantile hemispheric high-grade glioma [ 1 , 6 , 9 ], this fusion has not been described in pediatric GNTs to date.…”

Section: Introductionmentioning

confidence: 99%

Clinical, pathologic, and genomic characteristics of two pediatric glioneuronal tumors with a CLIP2::MET fusion

Chapman,

Greenwald,

Suddock

et al. 2024

acta neuropathol commun

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Integration of molecular data with histologic, radiologic, and clinical features is imperative for accurate diagnosis of pediatric central nervous system (CNS) tumors. Whole transcriptome RNA sequencing (RNAseq), a genome-wide and non-targeted approach, allows for the detection of novel or rare oncogenic fusion events that contribute to the tumorigenesis of a substantial portion of pediatric low- and high-grade glial and glioneuronal tumors. We present two cases of pediatric glioneuronal tumors occurring in the occipital region with a CLIP2::MET fusion detected by RNAseq. Chromosomal microarray studies revealed copy number alterations involving chromosomes 1, 7, and 22 in both tumors, with Case 2 having an interstitial deletion breakpoint in the CLIP2 gene. By methylation profiling, neither tumor had a match result, but both clustered with the low-grade glial/glioneuronal tumors in the UMAP. Histologically, in both instances, our cases displayed characteristics of a low-grade tumor, notably the absence of mitotic activity, low Ki-67 labeling index and the lack of necrosis and microvascular proliferation. Glial and neuronal markers were positive for both tumors. Clinically, both patients achieved clinical stability post-tumor resection and remain under regular surveillance imaging without adjuvant therapy at the last follow-up, 6 months and 3 years, respectively. This is the first case report demonstrating the presence of a CLIP2::MET fusion in two pediatric low-grade glioneuronal tumors (GNT). Conservative clinical management may be considered for patients with GNT and CLIP2:MET fusion in the context of histologically low-grade features.

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Molecular pathology and clinical implications of diffuse glioma

Cited by 16 publications

References 79 publications

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

Chronic stress as an emerging risk factor for the development and progression of glioma

Clinical, pathologic, and genomic characteristics of two pediatric glioneuronal tumors with a CLIP2::MET fusion

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